Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment/Arguments
The Amendment filed 6/4/2026 has been entered. Claims 1-15 remain pending on the application. Applicant’s amendments to the Specification and the Claims have overcome each and every objection to the Specification and 112(b) rejections to the Claims previously set forth in the Non-Final Office Action mailed 3/12/2026.
Applicant argues that the new claim amendments overcome the rejections of record. Examiner has updated the rejection using the same prior art to read on the new claim amendments. Concerning the limitation concerning a “large single-use device”, any finite size of the device in the prior art can be interpreted as “large” absent more specific numerical dimensions. In addition, the modification by Avallin sees a commercial scale separation unit being sterilized, which is interpreted as a large device for commercial production and bioprocessing. As for the connection line being rigid, Avallin is silent with respect to the rigidity of its connection line (which is separate from its recitation of flexible, deformable containers, contrary to Applicant’s argument) but its line would have a have finite rigidity which would read on rigid, absent a numerical standard for rigidity explicitly cited. The connection line is interpreted to have multiple fluid connections (since the insertion of a valve necessitates multiple fluid connections) that are ultimately connected to the filters/separation units in the column, linearly. Multiple branching connections have not been recited. Avallin also shows that its separation column contains several filters all in fluid communication with the rest of the system, which is interpreted as “reliably connected to one another”.
Applicant argues that Wootton is not adapted for large-scale commercial manufacturing devices, rigid connecting pipes, or dimensional stability challenges for multiple separation units. One of ordinary skill in the art would recognize that superheated steam would be effective for sterilizing non-gamma-sterilizable components regardless of size, pipe rigidity, and the number of filters. The only parameter that would matter is the amount of steam and the steam pressure. Furthermore, the primary reference already teaches using steam. Applicant further argues that using superheated steam risks plastic deformation especially when considering the deformable resin containers of Avallin. When modified by Avallin, the steam is not directed towards sterilizing the flexible container but rather the separation unit, so there is no inherent risk of plastic deformation for a separation column, as Avallin is silent with respect to the rigidity of the separation column
Applicant argues with respect to claims 9-10:
Mauzerall teaches a sterilization cabinet for medical instruments with a filtered vent that remains covered during sterilization. This is the opposite of the claimed method, in which the medium-contacting area passage is covered by a second closure before sterilization with superheated steam and until the superheated steam-sterilized separation unit is mounted, but the has at least one passage opening which can be selectively uncovered and closed.
Therefore, Applicant submits that Mauzerall teaches away from this feature.
It is unclear how this Mauzerall contradicts the claimed feature. It teaches that the filtered vent on the door remains covered during sterilization. This does not preclude covering the vent before sterilization not does it preclude removing the cover after the sterilized separation unit is mounted to something. Neither does it prevent the vent from being capable of being selectively uncovered and closed.
Applicant argues with respect to claims 12-13:
Hui teaches double packaging of medical instruments as a general sterility measure. However, Hui does not teach or suggest a first closure in the form of a blind cap, sterile connector, or jacket applied specifically to the fluid connections of a gamma-sterilizable rigid connecting pipe prior to gamma sterilization and maintained until assembly. The combination of cited references fails to disclose this specific feature and its function of protecting the medium-contacting area of the gamma-sterilizable component throughout the sterilization and transport process.
Claim 12 recites:
covered by a first closure, by a blind cap, a sterile connector OR a jacket.
The “or” operator means that only one of the features listed has to be read upon.
Applicant posits similar arguments for claims 3-5 as claim 1 and Examiner posits the same responses.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 6-8 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Boudreaux (US 20100198220 A1) in view of Avallin (WO 2018141701 A1) and Wootton (US 20120251386 A1).
Regarding claim 1, Boudreaux teaches a method of ensuring a microbiological purity of a large single-use device (par. 207: The devices disclosed herein can be designed to be disposed of after a single use; NOTE: absent a recitation of specific dimensions for what constitutes “large”, the devices of Boudreaux have finite dimensions that are then interpreted as large) for carrying out a biotechnological process (abstract: A surgical instrument),
wherein the large single-use device comprises at least one gamma-sterilizable component which is formed from materials suitable for a sterilization by gamma radiation
and at least one non- gamma-sterilizable unit which contains a material unsuitable for a sterilization by gamma radiation (par. 166: In any event, as a result of the above, a first portion, such as handle portion 6 and end effector 12 of surgical instrument 400, for example, and a second portion, such as module 402, for example, can undergo different sterilization processes and can be presented to an operating room, for example, in separately sterilized containers. Accordingly, a second portion having radiation-sensitive components can undergo a suitable non-radiation sterilization process and the first portion can undergo a radiation sterilization process without damaging the surgical instrument; par. 162: In various circumstances, the radiation can comprise gamma radiation; par. 163: while the selectively attachable portion, which can comprise electronic components and/or any other radiation-sensitive components, can be sterilized using any other suitable sterilization process, such as steam and/or ethylene oxide sterilization processes, for example),
and wherein the method comprises steps of:
(a) sterilizing at least one the gamma-sterilizable component by gamma radiation (par. 166: the first portion can undergo a radiation sterilization process without damaging the surgical instrument; par. 162: In various circumstances, the radiation can comprise gamma radiation;);
(b) protecting the medium-contacting area of the at least one gamma-sterilizable component by a sterile barrier (par. 166: In any event, as a result of the above, a first portion, such as handle portion 6 and end effector 12 of surgical instrument 400, for example, and a second portion, such as module 402, for example, can undergo different sterilization processes and can be presented to an operating room, for example, in separately sterilized containers);
(c) sterilizing the at least one non-gamma-sterilizable unit with steam (par. 163: while the selectively attachable portion, which can comprise electronic components and/or any other radiation-sensitive components, can be sterilized using any other suitable sterilization process, such as steam and/or ethylene oxide sterilization processes, for example);
(d) protecting the medium-contacting area of the at least one non-gamma-sterilizable
unit by a sterile barrier (par. 164: Prior to assembling module 402 to surgical instrument 400, module 402 can be sterilized and then placed within a sterile container. In certain embodiments, module 402 can be sterilized while already placed within a container);
(e) removing the sterile barriers; and
(f) mounting the gamma-sterilized component and the steam- sterilized unit in the large single-use device immediately after removing the sterile barriers (par. 171: In any event, one or more of the portions can remain sealed within, and/or only partially removed from, their enclosures when assembled to, operably engaged with, and/or otherwise suitably arranged with respect to the other portions of the surgical instrument).
But does not teach
in commercial manufacturing with a large medium throughput
and multiple separation units, the multiple separation units beinq at least one of filter capsules, chromatography columns and membrane adsorbers,
Wherein the non-gamma-sterilizable unit is a separation unit
both the at least one gamma-sterilizable component and the at least one non-gamma sterilizable separation unit each having a medium-contacting area that comes into contact with a process medium when the biotechnological process is carried out,
wherein the at least one gamma-sterilizable component comprises at least one rigid connecting pipe with fluid connections to which, after assembly of the large single- use device, multiple separation units are connected.
and wherein the steam is superheated.
Boudreaux already teaches sterilizing surgical instruments with two portions (par. 2: The present disclosure relates, in general, to surgical instruments suitable for use in sterile environments and, more particularly, to surgical instruments having a first portion and a second portion).
Avallin teaches a method for aseptic packing of a chromatography column (pg. 4 lines 14-15: Another object of the invention is to provide an improved method for aseptic packing of a chromatography column). This is interpreted to read on in commercial manufacturing with a large medium throughput (pg. 1 lines 5-7: In particular, it relates to methods and systems useful in the packing of chromatography columns for manufacturing-scale separation of biopharmaceuticals; NOTE: absent a recitation of specific numbers that would constitute a large medium throughput, the throughput of Avallin is finite and reads on a large medium throughput).
Avallin teaches a similar method comprising separating the column into two portions, one of which is sterilized via gamma sterilization and the other is not, before the two portions are assembled, wherein during usage, both portions contact a process medium (pg. 4 lines 16-30: This is achieved by a method for aseptic packing of a chromatography column with a separation resin comprising the steps of: filling a predetermined volume of separation resin and a volume of storage solution in a first container, said first container being a deformable, single-use container comprising an outlet port; sterilizing the first container comprising the separation resin by gamma radiation; sterilizing an interior of a chromatography column, said chromatography column being a second container; aseptically connecting the first container to the second container; - fluidizing the separation resin in the at least one first container to provide a resin slurry, said fluidizing being performed by mechanical interaction to the first container from an outside of the first container to provide a deformation of said first container; and transferring separation resin from the at least one first container to the second container by generating a pressure difference between an interior of the second container and an interior of the first container where the pressure is lower in the second container). Absent a recitation of a specific material or numerical estimate of the rigidity, the line connecting the two portions (Fig. 5: the line with a valve) would have a finite rigidity that reads on rigid.
There are multiple separation units comprised of filter capsules (Fig. 5: filters 107). Avallin teaches wherein the first and second portions have connecting lines for allowing fluid communication between the two (Fig. 5; abstract: fluidically connecting (S5) the outlet port (4') of the at least one first container to an inlet port (103) of the second container), which are then fluidly connected to the line (Fig. 5). The line has multiple fluid connections (such as those connected to the valve and the container) which are then in fluid communication with the filters 107 since a medium is able to be contained in and pass through this system.
However, Avallin does not teach more specific steps for the sterilization, wherein the method of Boudreaux is useful. Boudreaux also teaches sterilizing separate portions of a device with different sterilization methods, one of which involves gamma radiation, before assembling the two portions, but also provides for sterile containers for the two portions in order to preserve sterility after sterilization. Therefore, applying this method to chromatography columns would provide a more effective method of sterilizing chromatography columns.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux to sterilize two separate portions of a chromatography column, wherein the separation resin portion is sterilized via gamma sterilization, and the second portion is configured to receive the separation resin through a fluid connection line of finite rigidity with the first portion, wherein the second portion has multiple filters in fluid communication with the fluid connection line, as taught by Avallin, in order to provide an improved method of sterilizing chromatography columns that minimizes the risk of recontamination after sterilization.
Boudreaux modified by Avallin still does not teach wherein the steam is superheated.
Wootton teaches a method for sterilizing different portions of a device using different sterilization methods (par. 41: In an embodiment of a method for sterilizing complex devices, portions of a device are sterilized using at least one sterilization protocol while other portions of the device are sterilized by at least one protocol where the totality of sterilization protocols differs for different proportions of the device). Wootton teaches using superheated steam as one sterilization method (par. 74: Steam (e.g. heating at 100.degree. C. for 2 hours) and superheated steam (e.g. heating 125.degree. C. for 20 minutes) are examples of heated gases which may be used to transfer thermal energy to the device). Using superheated steam is advantageous because more thermal energy is transferred during sterilization, and higher temperatures would have greater sterilizing effect.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux to use superheated steam in its steam sterilization step, as taught by Wootton, in order to have a great sterilizing effect.
Regarding claim 2, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, but does not teach characterized in that a time period between removing a sterile barrier and mounting the associated gamma-sterilized component or the associated superheated steam-sterilized separation unit, respectively, is in each case shorter than four minutes.
Boudreaux already teaches wherein the separate portions of the device are only removed from their containers when they are to be assembled (par. 171: In any event, one or more of the portions can remain sealed within, and/or only partially removed from, their enclosures when assembled to, operably engaged with, and/or otherwise suitably arranged with respect to the other portions of the surgical instrument).
Furthermore, a mere change in proportion, even if it leads to better results, holds no patentable significance:
MPEP 2144.05.II.A: Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."
especially if it can be shown that the change in proportions can be done by one of ordinary skill in the art through routine optimization of a known result-effective variable (MPEP 2144.05.II.B: the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process).
In this, case, the less time elapses between the opening of the containers and the assembly, the less likely the connection areas are to be contaminated.
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the time period between removal of the portions from their containers and their assembly to be less than four minutes, with the reasonable expectation that the chances of contamination are minimized.
Regarding claim 6, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, and teaches characterized in that step (b) is performed before step (a) and/or step (d) is performed before step (c) (par. 164: Prior to assembling module 402 to surgical instrument 400, module 402 can be sterilized and then placed within a sterile container. In certain embodiments, module 402 can be sterilized while already placed within a container).
Regarding claim 7, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, and teaches characterized in that the sterile barrier for the superheated steam-sterilized separation unit comprises a closed envelope completely surrounding the separation unit (Fig. 60: container 301).
Regarding claim 8, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, and teaches characterized in that the envelope is formed from a watertight but water vapor-permeable nonwoven fabric (par. 162: such as container 301, for example, wherein, in certain embodiments, the container can be comprised of plastic, such as high density polyethylene fibers, or TYVEK; NOTE: Tyvek material is considered to read on a watertight but water vapor-permeable nonwoven fabric, in light of Applicant’s Specification pg. 14 line 29-32: The envelope is made of Tyvek®or a comparable material which, on the one hand, is watertight and can serve as a sterile barrier under normal ambient conditions but, on the other hand, is permeable to water vapor).
Regarding claim 14, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, and teaches characterized in that the sterile barrier for the gamma-sterilizable component comprises a closed primary packaging completely surrounding the component (Fig. 60; par. 6: The first portion can be positioned within the sealed package).
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Boudreaux modified by Avallin and Wootton in view of Mauzerall (WO 2020005844 A1).
Regarding claim 9, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, but does not teach characterized in that the medium-contacting area of the at last one non-gamma sterilizable separation unit is covered by a second closure, in particular the second closure being a lid before sterilization with superheated steam and until the superheated steam-sterilized separation unit is mounted, the second closure having at least one passage opening which can be selectively uncovered and closed.
Mauzerall teaches a sterilization cabinet for preserving the sterility of medical instruments and easy transfer between an autoclave (which would involve steam sterilization) and the place of usage (par. 5: At the end of the autoclaving cycle, cabinet 5 is removed from the autoclave, allowed to cool, and then moved to a storage space or directly to an operating room or other space for use in connection with a medical procedure. Sterilized cabinet 5 is kept closed until such time that its contents are required for a medical procedure. So long as cabinet 5 is kept closed, the contents will remain sterile, inasmuch as filters 50 prevent the passage of contaminants through vents 35 into the interior of the cabinet).
Boudreaux already teaches having a package around its steam sterilizable portion, but Mauzerall teaches wherein simply having one package would require additional time to inspect the package for damage and therefore an additional closure in the form of a sterilization cabinet is useful (par. 4: The trays are then removed from the autoclave, allowed to cool, and then stored until the contents are needed for a procedure. Prior to the use of the instruments and/or devices, additional man-hours are expended to inspect the wraps so as to ensure that there is no damage that might lead to the contents being deemed non-sterile).
Mauzerall teaches wherein the door to the sterilization cabinet has vents that can be covered up by a filter so that steam can enter (Fig. 46A: door 130, vent 430; abstract: at least one first filter covering the vent and a filter cover configured to hold the first filter against the vent). The door reads on a lid.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux modified by Avallin and Wootton to enclose the steam sterilizable portion inside a sterilization cabinet with a door with a vent that can be selectively covered by a filter, as taught by Mauzerall, to minimize the risk of recontamination after steam sterilization and to conveniently transfer the portion from the sterilizer to another place and/or to conveniently store the portion.
Regarding claim 10, Boudreaux modified by Avallin, Wootton, and Mauzerall teaches the method according to claim 1, as set forth above, and teaches characterized in that the at least one non-gamma-sterilizable separation unit has a a fluid connection (see Avallin modification in claim 1 rejection, wherein the second portion is configured to receive the separation resin by being fluidly connected with the first portion and reads on a separation unit since it is part of a chromatography column; see Applicant’s Specification pg. 1 lines 21-22: In the context of the present invention, a separation unit is understood to mean, e.g., a filter capsule, a chromatography column or a membrane adsorber) which is covered by a second closure (see Mauzerall modification in claim 9 rejection).
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Boudreaux modified by Avallin and Wootton in view of Hui (JP 2003070884 A).
Regarding claim 12, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, but does not teach characterized in that the medium-contacting area of the gamma-sterilizable component remains covered by a first closure, by a blind cap, a sterile connector or a jacket, prior to the sterilization by gamma radiation and until the gamma-sterilized component is mounted.
Boudreaux already teaches putting the instrument in a container made out of Tyvek (par. 162: a surgical instrument can be placed in a closed and sealed container, such as container 301, for example, wherein, in certain embodiments, the container can be comprised of plastic, such as high density polyethylene fibers, or TYVEK). Any additional closures of the same material would be a mere duplication of parts and would be advantageous for improving the preservation of sterility after sterilization.
Hui teaches a method of sterilizing medical instruments (abstract: To provide a method of effectively sterilizing tools; pg. 2 par. 3: Typically, the sterilization load includes any medical device). Hui teaches wherein sterilization loads are typically packaged in two closures (pg. 2 par. 3: Typically, the sterilization load includes any medical device placed in a package and / or pouch, such as a container, tray, barrier wrap, etc) which provides motivation to have two layers of sterility protection on a sterilization load.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux modified by Avallin and Wootton to have another packaging layer around each component before sterilization, as taught by Hui, in order to further decrease the chances of recontamination after sterilization is completed.
Since this modification merely duplicates the container, the duplicated container is also applied before gamma sterilization occurs (par. 164: Prior to assembling module 402 to surgical instrument 400, module 402 can be sterilized and then placed within a sterile container. In certain embodiments, module 402 can be sterilized while already placed within a container).
Regarding claim 13, Boudreaux modified by Avallin, Wootton, and Hui teaches the method according to claim 12, as set forth above, and teaches characterized in that the gamma-sterilizable component comprises a plurality of interconnectable manifold assemblies for connecting a plurality of separation units and/or at least one connecting hose line, wherein the gamma-sterilizable component includes at least one fluid connection that is covered by the first closure (see Avallin modification in claim 1 rejection concerning the fluid connection line, wherein the gamma-sterilizable portion has an outlet for fluid connection, and since it would be entirely enclosed in the container, the fluid connection would be covered).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Boudreaux modified by Avallin and Wootton in view of Hirschel (EP 3348284 A2).
Regarding claim 15, Boudreaux modified by Avallin and Wootton teaches the method according to claim 1, as set forth above, but does not teach characterized in that the superheated steam-sterilized separation unit and the gamma- sterilized component are mounted on a biological safety cabinet or in a clean room, preferably in an area of a clean room that is separated by walls.
Hirschel teaches a method for sterilizing an injection device which requires assembly after sterilization (abstract: A method for sterilizing a fluid path unit (25) for an injection device; par. 64: In the first two examples, the reservoir and the fluid path unit are both sterilized before entering the aseptic environment and are assembled in the aseptic environment which means that the space between the spike and the septum of the reservoir is also sterile). Hirschel teaches wherein assembly occurs in a clean room environment (par. 63: After filing, the sterile fluid paths are ready for assembly outside the aseptic environment, for example in the clean room). This is advantageous for minimizing the chances of recontamination. In addition, a clean room would have walls which separate an area of the clean room from an area outside the clean room.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux modified by Avallin and Wootton to have its assembly step take place in a clean room, as taught by Hirschel, in order to minimize the chances of recontamination.
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Boudreaux modified by Avallin and Wootton in view of Hui and Lin (AU 7241900 A).
Regarding claim 3, Boudreaux teaches a method of ensuring a microbiological purity of a large single-use device (par. 207: The devices disclosed herein can be designed to be disposed of after a single use; NOTE: absent a recitation of specific dimensions for what constitutes “large”, the devices of Boudreaux have finite dimensions that are then interpreted as large) for carrying out a biotechnological process (abstract: A surgical instrument),
wherein the single-use device comprises at least one gamma-sterilizable component which is formed from materials suitable for a sterilization by gamma radiation
and at least one non- gamma-sterilizable unit which contains a material unsuitable for a sterilization by gamma radiation (par. 166: In any event, as a result of the above, a first portion, such as handle portion 6 and end effector 12 of surgical instrument 400, for example, and a second portion, such as module 402, for example, can undergo different sterilization processes and can be presented to an operating room, for example, in separately sterilized containers. Accordingly, a second portion having radiation-sensitive components can undergo a suitable non-radiation sterilization process and the first portion can undergo a radiation sterilization process without damaging the surgical instrument; par. 162: In various circumstances, the radiation can comprise gamma radiation; par. 163: while the selectively attachable portion, which can comprise electronic components and/or any other radiation-sensitive components, can be sterilized using any other suitable sterilization process, such as steam and/or ethylene oxide sterilization processes, for example),
and wherein the method comprises steps of:
(a) sterilizing the at least one gamma-sterilizable component by gamma radiation (par. 166: the first portion can undergo a radiation sterilization process without damaging the surgical instrument; par. 162: In various circumstances, the radiation can comprise gamma radiation;);
(b) protecting the medium-contacting area of the at least one gamma-sterilizable component by a sterile barrier (par. 166: In any event, as a result of the above, a first portion, such as handle portion 6 and end effector 12 of surgical instrument 400, for example, and a second portion, such as module 402, for example, can undergo different sterilization processes and can be presented to an operating room, for example, in separately sterilized containers);
(c) sterilizing the at least one non-gamma-sterilizable unit with steam (par. 163: while the selectively attachable portion, which can comprise electronic components and/or any other radiation-sensitive components, can be sterilized using any other suitable sterilization process, such as steam and/or ethylene oxide sterilization processes, for example);
(d) protecting the medium-contacting area of the at least one non-gamma-sterilizable
unit by a sterile barrier (par. 164: Prior to assembling module 402 to surgical instrument 400, module 402 can be sterilized and then placed within a sterile container. In certain embodiments, module 402 can be sterilized while already placed within a container);
(f) removing the sterile barriers; and
(g) mounting the gamma-sterilized component and the steam- sterilized unit in the large single-use device immediately after removing the sterile barriers (par. 171: In any event, one or more of the portions can remain sealed within, and/or only partially removed from, their enclosures when assembled to, operably engaged with, and/or otherwise suitably arranged with respect to the other portions of the surgical instrument).
But does not teach
in commercial manufacturing with a large medium throughput
and multiple separation units, the multiple separation units beinq at least one of filter capsules, chromatography columns and membrane adsorbers,
Wherein the non-gamma-sterilizable unit is a separation unit
both the at least one gamma-sterilizable component and the at least one non-gamma sterilizable separation unit each having a medium-contacting area that comes into contact with a process medium when the biotechnological process is carried out,
wherein the at least one gamma-sterilizable component comprises at least one rigid connecting pipe with fluid connections to which, after assembly of the large single- use device, multiple separation units are connected.
and wherein the steam is superheated,
(e) additionally covering the medium-contacting area of the at least one gamma-sterilizable component with at least one first closure, and/or additionally covering the medium- contacting area of the at least one non-gamma-sterilizable separation unit with at least one second closure;
Boudreaux already teaches sterilizing surgical instruments with two portions (par. 2: The present disclosure relates, in general, to surgical instruments suitable for use in sterile environments and, more particularly, to surgical instruments having a first portion and a second portion).
Avallin teaches a method for aseptic packing of a chromatography column (pg. 4 lines 14-15: Another object of the invention is to provide an improved method for aseptic packing of a chromatography column). This is interpreted to read on in commercial manufacturing with a large medium throughput (pg. 1 lines 5-7: In particular, it relates to methods and systems useful in the packing of chromatography columns for manufacturing-scale separation of biopharmaceuticals; NOTE: absent a recitation of specific numbers that would constitute a large medium throughput, the throughput of Avallin is finite and reads on a large medium throughput).
Avallin teaches a similar method comprising separating the column into two portions, one of which is sterilized via gamma sterilization and the other is not, before the two portions are assembled, wherein during usage, both portions contact a process medium (pg. 4 lines 16-30: This is achieved by a method for aseptic packing of a chromatography column with a separation resin comprising the steps of: filling a predetermined volume of separation resin and a volume of storage solution in a first container, said first container being a deformable, single-use container comprising an outlet port; sterilizing the first container comprising the separation resin by gamma radiation; sterilizing an interior of a chromatography column, said chromatography column being a second container; aseptically connecting the first container to the second container; - fluidizing the separation resin in the at least one first container to provide a resin slurry, said fluidizing being performed by mechanical interaction to the first container from an outside of the first container to provide a deformation of said first container; and transferring separation resin from the at least one first container to the second container by generating a pressure difference between an interior of the second container and an interior of the first container where the pressure is lower in the second container). Absent a recitation of a specific material or numerical estimate of the rigidity, the line connecting the two portions (Fig. 5: the line with a valve) would have a finite rigidity that reads on rigid.
There are multiple separation units comprised of filter capsules (Fig. 5: filters 107). Avallin teaches wherein the first and second portions have connecting lines for allowing fluid communication between the two (Fig. 5; abstract: fluidically connecting (S5) the outlet port (4') of the at least one first container to an inlet port (103) of the second container), which are then fluidly connected to the line (Fig. 5). The line has multiple fluid connections (such as those connected to the valve and the container) which are then in fluid communication with the filters 107 since a medium is able to be contained in and pass through this system.
However, Avallin does not teach more specific steps for the sterilization, wherein the method of Boudreaux is useful. Boudreaux also teaches sterilizing separate portions of a device with different sterilization methods, one of which involves gamma radiation, before assembling the two portions, but also provides for sterile containers for the two portions in order to preserve sterility after sterilization. Therefore, applying this method to chromatography columns would provide a more effective method of sterilizing chromatography columns.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux to sterilize two separate portions of a chromatography column, wherein the separation resin portion is sterilized via gamma sterilization, and the second portion is configured to receive the separation resin through a fluid connection line of finite rigidity with the first portion, wherein the second portion has multiple filters in fluid communication with the fluid connection line, as taught by Avallin, in order to provide an improved method of sterilizing chromatography columns that minimizes the risk of recontamination after sterilization.
Boudreaux modified by Avallin still does not teach wherein the steam is superheated.
Wootton teaches a method for sterilizing different portions of a device using different sterilization methods (par. 41: In an embodiment of a method for sterilizing complex devices, portions of a device are sterilized using at least one sterilization protocol while other portions of the device are sterilized by at least one protocol where the totality of sterilization protocols differs for different proportions of the device). Wootton teaches using superheated steam as one sterilization method (par. 74: Steam (e.g. heating at 100.degree. C. for 2 hours) and superheated steam (e.g. heating 125.degree. C. for 20 minutes) are examples of heated gases which may be used to transfer thermal energy to the device). Using superheated steam is advantageous because more thermal energy is transferred during sterilization, and higher temperatures would have greater sterilizing effect.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux to use superheated steam in its steam sterilization step, as taught by Wootton, in order to have a great sterilizing effect.
Boudreaux modified by Avallin and Wootton still does not teach
(e) additionally covering the medium-contacting area of the gamma-sterilizable component with at least one first closure, and/or additionally covering the medium- contacting area of the non-gamma-sterilizable subunit with at least one second closure;
Boudreaux already teaches putting the instrument in a container made out of Tyvek (par. 162: a surgical instrument can be placed in a closed and sealed container, such as container 301, for example, wherein, in certain embodiments, the container can be comprised of plastic, such as high density polyethylene fibers, or TYVEK). Any further closures would be advantageous for improving the preservation of sterility after sterilization.
Hui teaches a method of sterilizing medical instruments (abstract: To provide a method of effectively sterilizing tools; pg. 2 par. 3: Typically, the sterilization load includes any medical device). Hui teaches wherein sterilization loads are typically packaged in two closures (pg. 2 par. 3: Typically, the sterilization load includes any medical device placed in a package and / or pouch, such as a container, tray, barrier wrap, etc) which provides motivation to have two layers of sterility protection on a sterilization load.
Lin teaches a method of sterilizing medical devices (abstract: A method for sterilizing medical devices and similar instruments). Lin teaches wherein sterile barriers having a pore size of 1 pm or less are commonly used for preventing recontamination after sterilization (pg. 41 lines 11-13: This is important, as filters, including ones made of Tyvek&, are often used in packaging of sterile articles to prevent re-contamination with bacteria. These filters generally have a pore size of 1 pm or less). This provides a means to satisfy the motivation of having two layers of sterility protection.
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boudreaux modified by Avallin and Wootton to have another packaging layer around each component before sterilization, wherein the layer has a pore size of 1 pm or less, as taught by Hui and Lin, in order to further decrease the chances of recontamination after sterilization is completed.
Regarding claim 4, Boudreaux modified by Avallin, Wootton, Hui, and Lin teaches the method according to claim 3, as set forth above, but does not teach characterized in that a time period between removing the respective sterile barrier and mounting the associated gamma-sterilized component provided with a first closure and/or the associated superheated steam-sterilized separation unit provided with a second closure is in each case shorter than three hours, and in that the time period between removing the first and second closures, respectively, and mounting the associated gamma-sterilized component and superheated steam-sterilized separation unit, respectively, is in each case shorter than two minutes.
Boudreaux already teaches wherein the separate portions of the device are only removed from their containers when they are to be assembled (par. 171: In any event, one or more of the portions can remain sealed within, and/or only partially removed from, their enclosures when assembled to, operably engaged with, and/or otherwise suitably arranged with respect to the other portions of the surgical instrument).
Furthermore, a mere change in proportion, even if it leads to better results, holds no patentable significance:
MPEP 2144.05.II.A: Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."
especially if it can be shown that the change in proportions can be done by one of ordinary skill in the art through routine optimization of a known result-effective variable (MPEP 2144.05.II.B: the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process).
In this, case, the less time elapses between the opening of both barriers and the assembly, the less likely the connection areas are to be contaminated.
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the time period between removal of the portions from their barriers and their assembly to be less than two minutes, with the reasonable expectation that the chances of contamination are minimized.
Regarding claim 5, Boudreaux modified by Avallin, Wootton, Hui, and Lin teaches the method according to claim 3, as set forth above, and teaches characterized in that at least one of the first and second closures constitutes a particle input reducing barrier having a clearance of at most 100 pm (see Lin modification in claim 3 rejection).
Allowable Subject Matter
Claim 11 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 11, Boudreaux modified by Avallin, Wootton, and Mauzerall teaches the method according to claim 10, as set forth above, and teaches wherein the sterile barrier comprises a closed envelope (par. 42: FIG. 60 is a view of a surgical instrument positioned within a sealed container), and wherein the method further comprises:
- attaching the second closure onto the fluid connection of the at least one non-gamma-sterilizable separation unit (see Mauzerall modification in claim 9 rejection);
- packing the at least one non-gamma-sterilizable separation unit into the closed envelope (par. 164: Prior to assembling module 402 to surgical instrument 400, module 402 can be sterilized and then placed within a sterile container. In certain embodiments, module 402 can be sterilized while already placed within a container);
- unpacking the superheated steam-sterilized separation unit from the closed envelope; and
- removing the second closure immediately prior to mounting the separation unit (par. 171: In any event, one or more of the portions can remain sealed within, and/or only partially removed from, their enclosures when assembled to, operably engaged with, and/or otherwise suitably arranged with respect to the other portions of the surgical instrument; NOTE: both the second closure and the container would be similarly removed after sterilization and before assembly since the second closure added by Mauzerall is already taught to be used during sterilization and must necessarily be removed in any assembly step), but does not teach
- uncovering a passage opening of the second closure if the passage opening is closed;
- sterilizing the packed separation unit with superheated steam with the passage opening uncovered;
- after sterilizing with superheated steam: closing the passage opening in the closed envelope;
This is because Mauzerall teaches wherein the vent is covered by a filter during sterilization and thus the vent/passage would be closed during sterilization rather than opened during sterilization and then closed afterwards.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.C./Examiner, Art Unit 1796
/KEVIN JOYNER/Primary Examiner, Art Unit 1799
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